N plus 3 Advanced Concept Studies for Supersonic Commercial Transport Aircraft Entering Service in the 2030-2035 Period

Boeing, with Pratt & Whitney, General Electric, Rolls-Royce, M4 Engineering, Wyle Laboratories and Georgia Institute of Technology, conducted a study of supersonic commercial aircraft concepts and enabling technologies for the year 2030-2035 timeframe. The work defined the market and environmental/regulatory conditions that could evolve by the 2030/35 time period, from which vehicle performance goals were derived. Relevant vehicle concepts and technologies are identified that are anticipated to meet these performance and environmental goals. A series of multidisciplinary analyses trade studies considering vehicle sizing, mission performance and environmental conformity determined the appropriate concepts. Combinations of enabling technologies and the required technology performance levels needed to meet the desired goals were identified. Several high priority technologies are described in detail, including roadmaps with risk assessments that outline objectives, key technology challenges, detailed tasks and schedules and demonstrations that need to be performed. A representative configuration is provided for reference purposes, along with associated performance estimates based on these key technologies

HSPVdb—the Human Short Peptide Variation Database for improved mass spectrometry-based detection of polymorphic HLA-ligands

T cell epitopes derived from polymorphic proteins or from proteins encoded by alternative reading frames (ARFs) play an important role in (tumor) immunology. Identification of these peptides is successfully performed with mass spectrometry. In a mass spectrometry-based approach, the recorded tandem mass spectra are matched against hypothetical spectra generated from known protein sequence databases. Commonly used protein databases contain a minimal level of redundancy, and thus, are not suitable data sources for searching polymorphic T cell epitopes, either in normal or ARFs. At the same time, however, these databases contain much non-polymorphic sequence information, thereby complicating the matching of recorded and theoretical spectra, and increasing the potential for finding false positives. Therefore, we created a database with peptides from ARFs and peptide variation arising from single nucleotide polymorphisms (SNPs). It is based on the human mRNA sequences from the well-annotated reference sequence (RefSeq) database and associated variation information derived from the Single Nucleotide Polymorphism Database (dbSNP). In this process, we removed all non-polymorphic information. Investigation of the frequency of SNPs in the dbSNP revealed that many SNPs are non-polymorphic “SNPs”. Therefore, we removed those from our dedicated database, and this resulted in a comprehensive high quality database, which we coined the Human Short Peptide Variation Database (HSPVdb). The value of our HSPVdb is shown by identification of the majority of published polymorphic SNP- and/or ARF-derived epitopes from a mass spectrometry-based proteomics workflow, and by a large variety of polymorphic peptides identified as potential T cell epitopes in the HLA-ligandome presented by the Epstein–Barr virus cells

Intermittent positive pressure ventilation with either positive end-expiratory pressure or high frequency jet ventilation (HFJV), or HFJV alone in human acute respiratory failure.

Continuous Positive Pressure Ventilation (CPPV), High-Frequency Jet Ventilation (HFJV), and a combination of HFJV with Intermittent Positive Pressure Ventilation (CV) were randomly compared in 13 critically ill patients with severe acute respiratory failure. Ventilatory settings were chosen in order to apply the same mean airway pressure (Paw) during the three modes. Respiratory frequencies were adjusted during CPPV (16 +/- 2 breaths/min) and HFJV (235 +/- 32 breaths/min) to achieve the same level of PaCO2 and were then combined during CV. All patients were heavily sedated during the study and had had peripheral and balloon-tipped pulmonary arterial catheters previously inserted. After a steady state at FIO2 1 in each mode of ventilation, hemodynamic and respiratory parameters were measured. A Paw of 13.8 +/- 2.9 mm Hg was applied to each patient by using a PEEP of 7.4 mm Hg during CPPV; a driving pressure of 2.9 +/- 0.2 bars and an I/E ratio of 0.43 during HFJV; and by combining HFJV, using a driving pressure of 1.2 +/- 0.3 bars with intermittent positive pressure ventilation during CV. There were no significant differences in any of the hemodynamic or respiratory parameters measured, except for a significant decrease in PaCO2 during CV when compared to CPPV or HFJV. We concluded that 1) arterial oxygenation and cardiac output depend mainly on Paw independent of the method used to increase Paw and 2) CV can improve CO2 elimination without increasing Paw.(ABSTRACT TRUNCATED AT 250 WORDS

Ventilatory effects of continuous epidural infusion of fentanyl.

The effects of a continuous epidural administration of fentanyl on pain and on ventilation were studied in eight patients scheduled for orthopedic surgery of the knee. In each subject, epidural fentanyl was given by a bolus dose of 1 microgram.kg-1, followed by a continuous infusion of 1 microgram.kg-1.h-1 over 18 hours. Ventilatory measurements were performed during quiet breathing and during CO2 stimulation tests before surgery. After surgery measurements were made before epidural administration of fentanyl; 1, 2, 5, 18 hours after the start of epidural fentanyl infusion; and 6 hours after its discontinuation. Adequate pain relief was achieved in all patients during fentanyl administration. No significant change in ventilation was noted during quiet breathing. The slope of the ventilatory response to CO2 (VE/PaCO2) decreased significantly from 1.46 +/- 0.2 to 0.75 +/- 0.1 L.min-1.mm Hg-1 (mean +/- SEM; P less than 0.05) one hour after the onset of fentanyl administration, and remained stable throughout the infusion. Eighteen hours after the onset of epidural fentanyl infusion, VE/PaCO2 was still 0.76 +/- 0.14 L.min-1.mm Hg-1. At the end of fentanyl administration, plasma fentanyl levels measured in six patients had progressively increased from 0.42 +/- 0.02 ng.ml one hour after the onset of the infusion to 1.54 +/- 0.19 ng.ml at the end of the infusion. These results suggest that a continuous epidural administration of fentanyl is a technique of analgesia that can provide adequate pain relief but which is associated with ventilatory depression. However, with the doses used in this study, the ventilatory depression remained moderate and of no demonstrable clinical consequence

Effects of high-frequency jet ventilation on arterial baroreflex regulation of heart rate.

Fifteen anesthetized mechanically ventilated patients recovering from multiple trauma were studied to compare the effects of high-frequency jet ventilation (HFJV) and continuous positive-pressure ventilation (CPPV) on arterial baroreflex regulation of heart rate. Systolic arterial pressure and right atrial pressure were measured using indwelling catheters. Electrocardiogram (ECG) and mean airway pressure were continuously monitored. Lung volumes were measured using two linear differential transformers mounted on thoracic and abdominal belts. Baroreflex testing was performed by sequential intravenous bolus injections of phenylephrine (200 micrograms) and nitroglycerin (200 micrograms) to raise or lower systolic arterial pressure by 20-30 Torr. Baroreflex regulation of heart rate was expressed as the slope of the regression line between R-R interval of the ECG and systolic arterial pressure. In each mode of ventilation the ventilatory settings were chosen to control mean airway pressure and arterial PCO2 (PaCO2). In HFJV a tidal volume of 159 +/- 61 ml was administered at a frequency of 320 +/- 104 breaths/min, whereas in CPPV a tidal volume of 702 +/- 201 ml was administered at a frequency of 13 +/- 2 breaths/min. Control values of systolic arterial pressure, R-R interval, mean pulmonary volume above apneic functional residual capacity, end-expiratory pulmonary volume, right atrial pressure, mean airway pressure, PaCO2, pH, PaO2, and temperature before injection of phenylephrine or nitroglycerin were comparable in HFJV and CPPV. Baroreflex regulation of heart rate after nitroglycerin injection was significantly higher in HFJV (4.1 +/- 2.8 ms/Torr) than in CPPV (1.96 +/- 1.23 ms/Torr).(ABSTRACT TRUNCATED AT 250 WORDS